The role of the pineal gland and its hormone, melatonin, has been difficult to define in humans, because the circulating levels of melatonin have been too low to measure. Recently, in collaboration with Dr. S. Markey of the LCS, we have developed a highly sensitive and specific (GC-MS) assay which requires less than 1 ml of human plasma, CSF, or urine. Since the development of this assay, melatonin research has been extended into two broad areas: (1) investigation of the pattern of secretion of melatonin as affected by circadian, seasonal, and menstrual rhythm; the effect of light, drugs, and sleep; and in various pathologic syndromes (precocious puberty, delayed onset of puberty, infertility, hypothalamic, pituitary, adrenal, and thyroid diseases, hypertension, breast and ovarian malignancies, as well as affective disorders and schizophrenia); (2) investigations of this hormone as a "marker" for (a) the biologic "clock", and (b) beta-adrenergic receptor function. We have found that sunlight, but not artificial light of normal intensity, suppresses melatonin secretion in humans, that melatonin is increased in mania and decreased in depression, that chronic tricyclic antidepressant treatment reduces melatonin, and that propranolol (a beta-adrenergic antagonist) abolishes melatonin secretion.